Title :

Exploring the trifluoromenadione core as a template to design antimalarial redox-active agents interacting with glutathione reductase

Author(s) :

Belorgey, Didier [Auteur]
École Européene de Chimie, Polymères et Matériaux de Strasbourg [ECPM]
Müller, Tobias [Auteur]
Heidelberg University
Vezin, Herve [Auteur]
Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement (LASIRE) - UMR 8516
Lanzer, Michael [Auteur]
Heidelberg University Hospital [Heidelberg]
Davioud-Charvet, Elisabeth [Auteur]
École Européene de Chimie, Polymères et Matériaux de Strasbourg [ECPM]

Journal title :

Organic & Biomolecular Chemistry

Abbreviated title :

Org. Biomol. Chem.

Volume number :

10

Pages :

4795-4808

Publisher :

Royal Society of Chemistry (RSC)

Publication date :

2012

ISSN :

1477-0539

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

Menadione is the 2-methyl-1,4-naphthoquinone core used to design potent antimalarial redox-cyclers to affect the redox equilibrium of Plasmodium-infected red blood cells. Exploring the reactivity of fluoromethyl-1,4-naph ...
Show more >Menadione is the 2-methyl-1,4-naphthoquinone core used to design potent antimalarial redox-cyclers to affect the redox equilibrium of Plasmodium-infected red blood cells. Exploring the reactivity of fluoromethyl-1,4-naphthoquinones, in particular trifluoromenadione, under quasi-physiological conditions in NADPH-dependent glutathione reductase reactions, is discussed in terms of chemical synthesis, electrochemistry, enzyme kinetics, and antimalarial activities. Multitarget-directed drug discovery is an emerging approach to the design of new antimalarial drugs. Combining in one single 1,4-naphthoquinone molecule, the trifluoromenadione core with the alkyl chain at C-3 of the known antimalarial drug atovaquone, revealed a mechanism for CF3 as a leaving group. The resulting trifluoromethyl derivative 5 showed a potent antimalarial activity per se against malarial parasites in culture.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement (LASIRE) - UMR 8516

Submission date :

2021-06-17T15:31:12Z
2021-10-05T11:03:15Z